AbstractAdipocytes are not merely organs for energy conservation but endocrine organs secreting a wide array of physiologically active substances, i.e., adipokines. Of these adipokines, adiponectin is known to exert anti-diabetic and anti-atherosclerotic effects via adiponectin receptors (AdipoR)s, AdipoR1 and AdipoR2. Adiponectin has also recently been shown to regulate longevity signaling thus prolonging lifespan. Therefore, the strategy for activating adiponectin/AdipoR signaling pathways are expected to provide a solid basis for the prevention and treatment of obesity-related diseases such as the metabolic syndrome, type 2 diabetes and cardiovascular disease, as well as for ensuring healthy longevity in humans.